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Theme 4
Imaging and Biomedical
Engineering
2017/18
2
Contents
1.4 Mechanisms of the dual epidemics of atrial fibrillation and heart failure: Image-based biophysical modelling approach ............................................................................................................................. 4
2.4 Hydrogels formed by peptide self-assembly as artificial extracellular matrices to study migration and control stem cell fate ...................................................................................................................... 5
3.4 Automated classification of prostate cancer phenotypes from magnetic resonance imaging: a deep learning approach powered by big data .................................................................................................... 6
4.4 Image guided drug delivery using Magnetoliposomes ............................................................................. 7
5.4 Investigations of the impact of EGFR/HER3 treatments on the cancer: immune stromal microenvironment interface, imaged by multiphoton and MR elastography techniques ................. 8
6.4 Neonatal multi-modal brain network features as biomarkers of altered neurodevelopment in high-risk infants ....................................................................................................................................................... 9
7.4 PET imaging of Anticancer Nanomedicines – A Theranostic Tool ..................................................... 10
8.4 Radiolabelling, evaluation and validation of a new 18F metomidate derivative for PET Imaging of Aldosteronomas ................................................................................................................................... 11
9.4 Developing in vivo traceable diagnostic and therapeutic IgE-like antibodies. ............................ 12
10.4 Hierarchically designed functionalized self-assembling peptide scaffolds for bone tissue engineering .................................................................................................................................................................. 14
11.4 In vivo myelin mapping with PET-MR imaging ...................................................................................... 15
12.4 Targeted radionuclide therapy: a new weapon in the war against microbial multi-drug resistance ...................................................................................................................................................................... 16
13.4 Improving stratification of valve stenosis through novel echocardiographic and computational methods ........................................................................................................................................... 17
14.4 Cancer stem cell theranostics: Copper compounds for both diagnostic PET imaging and chemotherapy ............................................................................................................................................................. 18
15.4 Radiobiological assessment of radionuclide pairs used in theranostic (imaging and therapy) approaches. ................................................................................................................................................ 19
16.4 Nano-scale engineering of the stem cell niche to generate iPS-hepatocytes for treatment of liver failure ................................................................................................................................................................... 21
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This theme focuses on the link between biomedical and physical sciences –
particularly physics, engineering and computational approaches. Clinical functional
and molecular imaging (MRI, PET, X-MR and PET-MR) is a major strength, along
with computational modelling and biomaterials (particularly in the Dental Institute).
Lead: Professor Phil Blower
When choosing a project from this catalogue in the funding section of the online application form
please enter: MRCDTP2016_Theme4
Deadline for application: Sunday 11th December 23:59
Shortlisted candidates will be contacted in mid-January and invited to an interview on one of the two
dates in February.
Interviews: 6th & 7th February 2017
The 2017/18 studentships will commence in September 2017.
For further Information or queries relating to the application process please contact
4
1.4 Mechanisms of the dual epidemics of atrial fibrillation and heart failure: Image-
based biophysical modelling approach
Co-Supervisor 1: Dr Oleg Aslanidi
Research Division or CAG: Imaging Sciences & Biomedical Engineering
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/oleg.aslanidi.html
Co-Supervisor 2: Prof Mark O’Neill
Research Division or CAG: Cardiovascular Clinical Academic Group
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/mark.oneill.html
Project Description:
Clinical treatment of complex and interlinked cardiovascular epidemics of atrial fibrillation (AF) and heart failure
(HF) in the same patient is extremely challenging, and understanding of AF-HF mechanisms is crucial for
designing efficient therapy. This project will explore the role of two major risk factors common in both AF and
HF − abnormal adrenergic response and fibrosis– and their contributions to the interlinked mechanisms of AF-
HF. Specifically, it will combine medical imaging [1] to quantify 3D atrial distributions of adrenergic innervation
and fibrosis in AF-HF patients and advanced biophysical modelling [2] to address the fundamental lack of
knowledge regarding effects of these risk factors on the electrophysiological function in AF-HF patients. The
novel knowledge will be applied to predict clinical therapy that can mitigate such mechanisms in a patient. Thus,
an interdisciplinary approach will be applied to create an image-based computational workflow for the
characterisation of AF-HF patient state, and ultimately for tailoring therapy to the need of a patient.
MRes: Computational study of AF-HF electrophysiology; Year 1: PET and MRI data acquisition for quantify
3D atrial innervation and fibrosis; Year 2: Development of biophysical models integrating the imaging and
electrophysiological data; Year 3: Model validation against AF-HF patient electro-anatomical mapping data and
prediction of optimal therapy. Supervisors: OA will provide expertise in biophysical modelling and imaging of
the atria and help the student develop computational skills; MON will provide expertise in electro-anatomical
mapping of AF-HF patients and support the student to learn about ablation therapy. Candidate: Degree in
Biomedical Engineering or related discipline.
Two representative publications from supervisors:
[1] Harrison JL, Sohns C, Linton NW, Karim R, Williams SE, Rhode KS, Gill J, Cooklin M, Rinaldi CA, Wright
M, Schaeffter T, Razavi RS, O'Neill MD. Repeat left atrial catheter ablation: Cardiac magnetic resonance
prediction of endocardial voltage and gaps in ablation lesion sets. Circulation Arrhythmia & Electrophysiology
2015; 8(2): 270-78. DOI: 10.1161/circep.114.002066.
[2] Morgan R, Colman MA, Chubb H, Seemann G, Aslanidi OV. Slow conduction in the border zones of patchy
fibrosis stabilizes the drivers for atrial fibrillation: Insights from multi-scale human atrial modeling. Frontiers in
Physiology 2016; 7: 474. DOI: 10.3389/fphys.2016.00474.
5
2.4 Hydrogels formed by peptide self-assembly as artificial extracellular matrices to
study migration and control stem cell fate
Co-Supervisor 1: Dr Eileen Gentleman
Research Division or CAG: Dental Institute
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/eileen.gentleman.html
Co-Supervisor 2: Dr Cecile Dreiss
Research Division or CAG: Institute of Pharmaceutical Sciences
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/cecile.dreiss.html
Project description:
The extracellular matrix (ECM) is organised in space and time through molecular self-assembly, lending it
important properties to direct stem cell differentiation and control migration, both of which are fundamental in
health and disease. Current 3D scaffold designs do not replicate the self-assembled, dynamic nature of the native
ECM and so are poor models for studying these processes. 3D in vitro models that mimic the dynamic ECM
have the potential to reveal fundamental insights in development, cancer metastasis and wound healing, as well
as direct stem cell differentiation for tissue engineering. Recent studies have shown that peptides that self-
assemble into fibrillar nanostructures like the ECM constantly and dynamically disassemble and re-assemble.
For this interdisciplinary project, we are looking for a motivated student with a background in either chemistry,
physics, cell biology or engineering to build on this discovery and synthesise 3D hydrogels that form by peptide
self-assembly. This platform system will allow us to systematically control 3D stiffness, the spatial distribution of
cell adhesive ligands, and the underlying molecular interactions. We will then structurally and mechanically
characterise the hydrogels and use them to explore key biological questions in directing stem cell fate for
regenerative medicine and mechanically controlling cell migration. Specifically, we will:
1. Produce hydrogels by synthesising peptides that form dimers (characterised by circular dichroism,
isothermal calorimetry), conjugate them with polymers, and determine their nanoscale structure and
mechanical properties using small-angle neutron scattering, atomic force microscopy, and rheology.
(year 1/2)
2. Encapsulate fluorescently tagged human mesenchymal stem cells and highly migratory cells (e.g.
neural crest, dermal fibroblasts) within hydrogels and monitor their differentiation and/or migration
using molecular biology, immunohistochemistry, and live cell multi-photon microscopy techniques.
We will also investigate dynamic processes using super-resolution microscopy (STORM), single
molecule fluorescence localisation and force microscopy. (year 2/3)
Two representative publications from supervisors:
[1] Gentleman, E. et al. Comparative materials differences revealed in engineered bone as a function of cell-
specific differentiation. Nat. Mater. 8:763-70 doi:10.1038/nmat2505 (2009).
[2] Walters, N. J. & Gentleman, E. Evolving insights in cell–matrix interactions: Elucidating how non-
soluble properties of the extracellular niche direct stem cell fate. Acta Biomater. 11:3-16
doi:10.1016/j.actbio.2014.09.038 (2015).
6
3.4 Automated classification of prostate cancer phenotypes from magnetic resonance
imaging: a deep learning approach powered by big data
Co-Supervisor 1: Giovanni Montana
Research Division or CAG: Biomedical Engineering
E-mail: [email protected]
Website: https://wwwf.imperial.ac.uk/~gmontana/
Co-Supervisor 2: Gary Cook
Research Division or CAG: Cancer Imaging
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/gary.cook.html
Project description:
Determining clinically significant prostate cancer remains a major challenge. The aggressiveness of prostate
cancer is routinely assessed using the histological biopsy Gleason score (GS). However, the GS measurements
determined through biopsy suffer from sampling bias and cancer heterogeneity, and often differ from
measurements obtained following radical prostatectomy and those made between immediate repeat biopsies.
There is an unmet clinical need to improve non-invasive characterisation of prostate cancer, reducing the need
for as many biopsy cores and improving treatment planning that current standard multi-parametric MRI
(mpMRI) only partially addresses.
In this project we will develop a mpMRI-based predictive system for fully-automated prostate cancer profiling,
that leverages “big data” and recent developments in “deep learning”. An initial population of 5,000 confirmed
prostate cancer patients treated at Guy’s and St Thomas’ NHS Trust over the last 8 years has been identified
with full electronic clinical records, including mpMRI and histopathology.
In Year 1 we will build on prior work in natural language processing for entity detection in radiological texts
(Cornegruta et al 2016) and extract relevant clinical indicators such as GS from radiological reports. In Year 2
we will develop a deep learning algorithm for the fully automated detection of the prostate gland and malignant
tumours from raw MR images. In Year 3 we will develop and validate state-of-the-art deep neural networks (e.g.
Ypsilantis at al 2015) for learning mpMRI imaging features that are highly predictive of the measurements. In
Year 4 we will produce a user friendly software application to enable clinicians to adopt the methodology.
Two representative publications from supervisors:
[1] Ypsilantis P., Siddique M., Sohn H., Davies A., Cook G., Goh V., and Montana G. (2015) Predicting
response to neoadjuvant chemotherapy with PET imaging using convolutional neural networks. PloS One.
[2] Cornegruta S., Bakewell R., Withey S., and Montana G. (2016) Modelling Radiological Language with
Bidirectional Long Short-Term Memory Networks. 7th International Workshop on Health Text Mining and
Information Analysis
7
4.4 Image guided drug delivery using Magnetoliposomes
Co-Supervisor 1: Dr Maya Thanou
Research Division/Department or CAG: Institute of Pharmaceutical Science
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/maya.thanou.html
Co-Supervisor 2: Dr Po-Wah So
Research Division/Department or CAG: Institute of Psychiatry, Psychology & Neuroscience
Email: [email protected]
Website: http://https://kclpure.kcl.ac.uk/portal/po-wah.so.html
Name of Collaborating Clinicians: Professor Afshin Gangi, Professor Michael Douek
Research Division/Department or CAG: Perinatal Imaging & Health
Email: [email protected], [email protected]
Website:https://kclpure.kcl.ac.uk/portal/afshin.gangi.html,
https://kclpure.kcl.ac.uk/portal/michael.douek.html
Project description:
We have successfully developed MRI/optical bimodal liposomes that encapsulate a series of anticancer agents.
The liposomes have thermosensitive properties and release the drug when activated by local hyperthermia.
Liposomes’ biodistribution in tumours is monitored via imaging, when liposomes are detected in the tumour,
hyperthermia is applied using Focused Ultrasound. Focal hyperthermia induces the liposomes to become leaky
and release their therapeutic cargo instantly within the tumour only. This method can lead to maximum dosing
of anticancer agent. MRI guided focused ultrasound is a technique currently available in the clinic (Prof. Gangi-
KCL). We aim now to prepare liposomes for MRI guided Focused Ultrasound technique (2 patents PCT 2016-
King’s Commercialisation Institute).
Milestone 1: NIRF/MRI labelled magnetoliposomes 1) The student will be preparing thermosensitive
liposomes labelled with NIRF probes loaded with super-paramagnetic iron oxide nanoparticles
(SPIONs) for MRI. The student will test the imaging properties of these liposomes in solutions.
Milestone 2: The student will be trained on preparing drug containing magnetoliposomes and
investigating drug release, pharmacokinetics and biodistribution by MRI in mice tumour models.
Milestone 3: The student will be studying methods of SPION imaging by MRI and activating these
magnetoliposones using MRIgFUS.
Milestone 4: In vivo Proof of Concept experiments (Home office project license PPL/7008687) in mice
using optical imaging-FUS (preclinical) and MRIgFUS (Clinical)
Prof Phillip Blower and Dr Rafa Torres will be collaborating (part of the supervisory team) to provide expertise
on iron oxide nanoparticles as well as the potential to prepare these magnetoliposomes for PET/MRI imaging.
This project is suitable for students of Chemistry, Pharmacy, Material Sciences, and Bioengineering.
Two representative publications from supervisors:
[1] Thermosensitive, Near-Infrared-Labeled Nanoparticles for Topotecan Delivery to Tumors
Rosca, E. V., Wright, M., Gonitel, R., Gedroyc, W., Miller, A. D. & Thanou, M. May 2015 In : Molecular
Pharmaceutics. 12, 5, p. 1335-1346
[2] Biomodal paramagnetic and fluorescent liposomes for cellular and tumor magnetic resonance imaging.
Kamaly N, Kalber T, Ahmad A, Oliver MH, So PW, Herlihy AH, Bell JD, Jorgensen MR, Miller AD. Jan 2008
In : Bioconjug Chem. 19(1): 118-29.
8
5.4 Investigations of the impact of EGFR/HER3 treatments on the cancer: immune
stromal microenvironment interface, imaged by multiphoton and MR elastography
techniques Co-Supervisor 1: Prof. Tony Ng
Research Division or CAG: Cancer & Randall
E-mail: [email protected]
Website: http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/cell/ng/ngtony.aspx
Co-Supervisor 2: Prof. Ralph Sinkus
Research Division or CAG:
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/ralph.sinkus.html
Project description:
A bedside-to-bench study, which is related to an ongoing Pan-European Phase II translational clinical trial, is
proposed to investigate the impact of EGFR/HER3 targeting on the immune stromal microenvironment
remodeling in head and neck cancers. The candidate who should have a cell biology/biophysics background will
take part in our ongoing work on therapy-induced ErbB/HER receptor rewiring in cancer cells/tissues/exosome.
The Skill training #1 will be on “Imaging the HER receptor dimer network both physiologically and under
therapeutic pressure; and its mechanistic linkage to unfolded protein response (UPR) which we have shown to
occur in response to EGFR treatments, in our established preclinical head and neck tumour mouse model
(Multiphoton Cell Imaging Techniques in T Ng’s lab, as applied to ErbB/HER receptors: Current Biology
19;1788 (2009), Science Signaling 7: ra78 and 7: ra29 (2014), ONCOTARGET 7: 51012 (2016), ACS Nano
(2016) (Year 1 objective).
Only 30-40% of patients respond to immune checkpoint therapies in various cancer types and currently there
are no reliable predictive tools for assigning treatment. We propose to undertake a multidisciplinary approach,
including the use of MR elastography techniques (Skill training #2) to probe the tumour microenvironment
regarding collagen remodelling (Magnetic resonance in medicine 58: 1135 (2007), Phys. Rev. Lett. 115, 094301
(2015)), to study this crosstalk mechanism The candidate will learn from Professor Sinkus how to use the MRI-
based elastography method to quantify the biomechanical nature of the cancer stromal tissues in whole animals
treated with EGFR treatments which will affect the immune stromal microenvironment (Year 2 objective).
The goal is to unravel the scientific mechanisms which may help clinicians to combine immunotherapeutics with
molecularly targeted approaches, including the use of anti- HER therapeutics; in order to improve treatment
efficacy; supported by imaging human samples (tissues/blood exosomes) from the Phase II trial (Year 3/4
objective).
Two representative publications from supervisors:
[1] Sinkus R, Siegmann K, Xydeas T, Tanter M, Claussen C, Fink M (2007) MR elastography of breast
lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR
mammography. Magnetic resonance in medicine 58: 1135-1144
[2] Kiuchi T, Ortiz-Zapater E, Monypenny J, Matthews DR, Nguyen LK, Barbeau J, Coban O, Lawler K,
Burford B, Rolfe DJ, de Rinaldis E, Dafou D, Simpson MA, Woodman N, Pinder S, Gillett CE, Devauges V,
Poland SP, Fruhwirth G, Marra P, Boersma YL, Pluckthun A, Gullick WJ, Yarden Y, Santis G, Winn M,
Kholodenko BN, Martin-Fernandez ML, Parker P, Tutt A, Ameer-Beg SM, Ng T (2014) The ErbB4 CYT2
variant protects EGFR from ligand-induced degradation to enhance cancer cell motility. Science signaling 7:
ra78
9
6.4 Neonatal multi-modal brain network features as biomarkers of altered
neurodevelopment in high-risk infants
Co-Supervisor 1: Professor Serena Counsell
Research Division or CAG: Imaging Sciences & Biomedical Engineering
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/serena.counsell.html
Co-Supervisor 2: Dr Dafnis Batalle
Research Division or CAG: Imaging Sciences & Biomedical Engineering
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/dafnis.batalle.html
Name of Collaborating Clinician: Professor David Edwards
Research Division or CAG: Imaging Sciences & Biomedical Engineering and Neonatal Unit
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/david.edwards.html
Project description:
Disrupted perinatal brain development is associated with life-long cognitive and behavioural impairment, which
imparts a significant burden to the individual, their families and society. There is an urgent need to identify
impairments in brain development in the neonatal period, when intervention with appropriate therapies may be
possible. Sensitive biomarkers are required to assess the effects of these treatments at an early stage. Powerful
new magnetic resonance imaging (MRI) methods are becoming available and it is likely that a multi-modal
imaging approach will be both more sensitive to injury and more closely correlated to subsequent performance
than approaches that rely on any single imaging technique. This project will use brain connectivity analysis of
multi-modal MRI data obtained in the early neonatal period to develop early imaging biomarkers of
neurodevelopmental performance in children who are at high-risk of impairment.
Specific Aims
Year 1: (i) Generate structural and functional connectivity characteristics from multi-modal (diffusion and
functional) MR data. (ii) Correlate imaging results with neurodevelopmental performance at 2 and 4.5 years,
and with perinatal clinical variables (for example respiratory morbidity, gestation at birth).
Year 2: Develop machine-learning models allowing blind prediction of altered neurodevelopment.
Year 3: Determine generalizability of the biomarkers obtained by assessing an independent neonatal
neuroimaging dataset.
Skills Training
The project will suit a student with a background in computer science, physics or mathematics. The student will
receive training in image analysis including; graph theory analysis, biophysical modelling of diffusion MRI data
and neonatal MRI.
Two representative publications from supervisors:
[1] Ball G, Aljabar P, Zebari S, Tusor N, Arichi T, Merchant N, Robinson EC, Ogundipe E, Rueckert D,
Edwards AD, Counsell SJ. Rich-club organisation of the newborn human brain. Proc Natl Acad Sci USA 2014
20;111(20):7456-61. doi: 10.1073/pnas.1324118111. Epub 2014 May 5.
[2] Batalle D, Muñoz-Moreno E, Tornador C, Bargallo N, Deco G, Eixarch E, Gratacos E; Altered resting-
state whole-brain functional brain networks of neonates with intrauterine growth restriction; Cortex, 2016, 77,
pp. 119-131
10
7.4 PET imaging of Anticancer Nanomedicines – A Theranostic Tool Co-Supervisor 1: Dr Rafael T. M. de Rosales
Research Division or CAG: Imaging Sciences & Biomedical Engineering
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/rafael.torres.html
Co-Supervisor 2: Prof Bob Hider
Research Division or CAG: Pharmaceutical Science
Email: [email protected]
Website: http://www.kcl.ac.uk/lsm/research/divisions/ips/research/chembio/Staff/Hider.aspx
Project description:
Nanomedicine has the potential to help personalize cancer treatments and reduce side effects of therapeutic
drugs. While some progress has been made toward the latter goal, customized treatments are still hard to come
by. Our research group is interested in developing method for seeing where certain cancer drugs accumulate in
the body in order to better treat patients.
Recent research has shown how complicated is to customize treatment for cancer patients. As one might expect,
the same drug will accumulate in tumors at varying concentrations in patients with different cancers, but also
those with the same kind of cancer. To evaluate which patients would benefit nanomedicinal treatment, it would
be helpful to determine if a drug will target the right places at effective concentrations. We want to address this
challenge using PET imaging, an imaging technique allow us to detect and quantify areas of nanomedicine
uptake with high accuracy and spatial resolution compared to other medical imaging techniques.
In this project we will build up from recent work in the group where we developed a simple method to attach
PET labels to liposomal nanomedicines containing metal-binding anticancer drugs (1). We will extend this
method to nucleic acids (e.g. RNAi or DNA) and metal-binding molecules used in cancer chemotherapy (Y1-
2, nanomedicine synthesis– supervised by RTMR/RH). After radiolabeling optimisation (Y2-3, radiochemistry
– supervised by RTMR), the nanomedicines will be tracked using positron emission tomography (PET) to see
where they go within the body. Imaging with PET in mouse models of breast, ovarian and prostate cancer (Y2-
4, PET imaging – supervised by RTMR/RH) will allow us to see and quantify if the drug accumulates in tumors
and metastases. The final aim is to prove that out PET imaging technology allows the prediction of therapeutic
outcomes.
Two representative publications from supervisors:
[1] S. Edmonds, et al. Exploiting the Metal Chelating Properties of the Drug Cargo for In Vivo Positron
Emission Tomography Imaging of Liposomal Nanomedicines, ACS Nano, 2016, IN PRESS
(http://pubs.acs.org/doi/abs/10.1021/acsnano.6b05935 ) - Available from 28th October
[2] D. Berry et al. Efficient bifunctional gallium-68 chelators for positron emission tomography:
tris(hydroxypyridinone) ligands, Chemical Communications, 2011, 47, 7068.
(http://pubs.rsc.org/en/content/articlehtml/2011/cc/c1cc12123e)
11
8.4 Radiolabelling, evaluation and validation of a new 18F metomidate derivative for
PET Imaging of Aldosteronomas
Co-Supervisor 1: Salvatore Bongarzone
Research Division or CAG: Division of Imaging Sciences and Biomedical Engineering
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/salvatore.bongarzone.html
Co-Supervisor 2: Andrew Webb
Research Division or CAG: Cardiovascular Division
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/andrew.1.webb.html
Project description:
Scientific basis: Primary hyperaldosteronism accounts for 6-15% of hypertension - the single biggest contributor
to global morbidity and mortality. Whilst ~50% of patients with hyperaldosteronism have unilateral aldosterone-
producing adenomas, only a minority have curative surgery, as current identification is poor. Microadenomas
(<1cm) are often missed on CT/MRI and biochemical/endocrine tests. The rise of PET-CT, specific/sensitive
imaging technique for the detection of tumors, has yielded great interest towards developing new diagnostic
PET radiotracer. The PET radiotracer 11C-Metodomidate (MTO), a potent inhibitor of CYP11B2 beta
hydroxylase, is selectively taken up by active adenomas. However, [11C]Metomidate’s short 20-min half-life
limits its use to PET sites with a cyclotron. The ability of MTO to selectively target adrenocortical lesions has
presented a molecular template upon which modifications can be made to greatly enhance its properties.
Translational aspect: we have developed a longer-lived fluorine-18-labelled metomidate-PET radiotracer
([18F]FAMTO, 2-hour half-life) to allow lower-cost imaging for many more patients locally and nationally
through wider distribution.
The PhD candidate will pursue optimization of the synthesis, in vitro and in vivo characterization of
[18F]FAMTO allowing its translation to pre-clinical and clinical evaluation.
First Year:
Aim: Basic understanding and practices of PET radiochemistry and PET radiopharmacology.
Skills training: Radiotracer design, 18F-radiochemistry, Radio-analytical and purification techniques. Contact
with Hypertension clinics for clinical perspective.
Second Year:
Aim: In vitro characterisation of [18F]FAMTO.
Skills training: Radioligand binding assays, human and animal tissue sections and autoradiography.
Third and Fourth Years:
Aim: In vivo characterisation of [18F]FAMTO.
Skills training: In vivo techniques and ethics: microPET, metabolite analysis, tracer administration, personal
Home Office Licensee training. Further clinical contact.
Two representative publications from supervisors:
[1] [11C]CO2 to [11C]CO Chemical Conversion: A Novel Route for [11C]Carbonylation Reactions. Taddei,
C*; Bongarzone S*, Haji Dheere A, Gee A D. ChemComm (2015) 51, 59, 11795-11797
[2] Omar SA, Fok H, Tilgner KD, Nair A, Hunt J, Jiang B, Taylor P, Chowienczyk P, Webb AJ.
Paradoxical normoxia-dependent selective actions of inorganic nitrite in human muscular conduit arteries and
related selective actions on central blood pressures. Circulation. 2015;131:381-389.
12
9.4 Developing in vivo traceable diagnostic and therapeutic IgE-like antibodies.
Co-Supervisor 1: Dr Gilbert Fruhwirth
Research Division/Department or CAG:Imaging Sciences / Imaging Chemistry and Biology
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/gilbert.fruhwirth.html
Co-Supervisor 2: Dr Sophia Karagiannis
Research Division/Department or CAG: Skin Sciences / St John’s Institute of Dermatology
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/sophia.karagiannis.html
Name of Collaborating Clinician: Prof. James F Spicer
Research Division/Department or CAG: Division of Cancer Studies, Faculty of Life Sciences and Medicine
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/james.spicer.html
Project description:
Human immunity produces several antibody classes. IgE class antibodies are the least abundant with very short
serum half-lives, but the longest residence times in target tissues. Specific glycosylation patterns on their Fc
domains may be responsible for their serum properties and this has hampered their diagnostic and therapeutic
use [1].
Combining our expertise in IgE biology/immunology and in vivo tumour imaging/radiochemistry, we will
develop optimised in vivo-traceable diagnostic and therapeutic IgE-like molecules with favourable serum half-
lives. We will employ molecular biology to modify: (i) glycosylation sites on antibodies and (ii) glycosylation
enzymes in the corresponding expression systems. We will also reconstitute separately synthesised antibody
fragments to generate chimeric molecules for diagnostic imaging.
Objective rotation+Yr1/2: Alter IgE Fc glycosylation using genetic approaches; determine resultant
glycosylation patterns by immunoblotting and carbohydrate analysis (detection, digestion, mass
spectrometry, fluorimetry).
Objective Yr2/3: Radiolabel IgE glycovariants/chimera, determine their in vivo distribution,
pharmacokinetics/dynamics in an in vivo-traceable melanoma model (radionuclide/CT-fluorescence
multi-scale imaging). Combining traceable tumour cells and IgE-antibodies will allow full preclinical
cross-validation (distribution, redistribution, efficacy).
Objective Yr3: Determine optimised IgE glycovariant functions by characterizing antigen and receptor
binding properties (e.g. ELISA, Biacore, flow cytometry), IgE-mediated signalling (diagnostics and
safety) and tumour cell killing (therapeutic aspect).
These will form the basis for developing IgE immunodiagnostics and immunotherapeutics. This studentship
covers basic and translational research through close interactions with the Comprehensive Cancer Imaging
Centre (KCL&UCL) and St. John’s Institute of Dermatology and benefits from multi-disciplinary experience
in molecular biology, cancer immunology, and multi-modal whole-body in vivo imaging.
Student Background:
Biochemistry, Molecular Biology/Biotechnology, Cell Biology or similar. Also, molecular or life sciences or
related BSc degrees (e.g. chemical biology, pharmacology etc) plus a relevant Master-level degree would be a
good fit.
Two representative publications from supervisors:
13
[1] Josephs et al (2014) MAbs 6:1, 54-72. doi: 10.4161/mabs.27029. Review. PMID: 24423620
[2] Fruhwirth et al (2014) J Nucl Med 55:4, 686-94. doi: 10.2967/jnumed.113.127480. PMID: 24604910
14
10.4 Hierarchically designed functionalized self-assembling peptide scaffolds for
bone tissue engineering Co-Supervisor 1: Sanjukta Deb
Research Division or CAG: Tissue Engineering & Biophotonics
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/sanjukta.deb.html
Co-Supervisor 2: Lucy Di Silvio
Research Division or CAG: Tissue Engineering & Biophotonics (TEB)
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/lucy.di_silvio.html
Project description:
A major challenge in the development of engineered bone scaffolds is the ability to vascularize and integrate with
the host tissue. Vascularization is important since blood vessels 1) mediate delivery and disposal of nutrients and
metabolic waste (mass transfer) and 2) act as ‘railways’ for the recruitment of osteogenic precursors in order to
promote angiogenensis and osteogenesis. Bioresorbable, biomimetic scaffolds can be tailored to provide
biochemical cues to support and enhance bone tissue regeneration. The Deb group has developed a novel
composite bone scaffold based on a calcium phosphate elastomeric hydrogel composite with favourable
biomechanical and mineralization characteristics. Total resorption has been demonstrated in an in-vivo rabbit
mandibular model in 8 weeks.
The Di Silvio group, is studying the biological enhancement of scaffolds using a novel synthetic self-assembling
peptides (SAP) with potential to exert pro angiogenic/osteogenic effects. In-vitro and in-vivo studies to date,
have demonstrated biocompatibility and an enhancement in cellular response. This project will explore the
angiogenic and bone regenerative capacity of the newly designed bone scaffold in combination with the SAP as
the bioactive molecule, and also in presence of ions such as zinc and strontium, known to promote bone healing.
Year 1: Design and characterisation of the polymer networks
Year 2: Encapsulation of SAP within the polymeric networks, composite formulation and evaluation of
biological activity with in vitro cell culture techniques
Year 3: The effect on mechanical loading and perfusion using a bioreactor
Year 4: In vivo studies to test bone regenerative potential of the constructs
Two representative publications from supervisors:
[1] L. Rojo, B. Gharibi, R. McLister, B. J. Meenan and S. Deb; Self-assembled monolayers of alendronate
on Ti6Al4V alloy surfaces enhance osteogenesis in mesenchymal stem cells. Nature Scientific Reports (NPG)
2016 Scientific Reports | 6:30548 | DOI: 10.1038/srep30548
[2] Buranawat, Borvornwut; Di Silvio, Lucy; Deb, Sanjukta; et al. Evaluation of a beta-Calcium
Metaphosphate Bone Graft Containing Bone Morphogenetic Protein-7 in Rabbit Maxillary Defects, Journal of
Periodontology, 85: 298-307, 2014
15
11.4 In vivo myelin mapping with PET-MR imaging
Co-Supervisor 1: Federico E. Turkheimer, PhD
Research Division or CAG: Dept. of Neuroimaging, Neuroscience Division
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/federico.turkheimer.html
Co-Supervisor 2: Mattia Veronese, PhD
Research Division or CAG: Dept. of Neuroimaging, Neuroscience Division
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/mattia.veronese.html
Project description:
In the brain and spinal cord, nerves are covered by an insulating myelin sheath that allows fast transmission of
electrical impulses and protects the nerve. In demyelinating diseases, the normal myelin sheath is damaged and
patches of demyelination occur causing many neurological symptoms such as paralysis, sensory changes and
blindness. Re-myelination can happen spontaneously or can be induced by compounds acting on
oligodendrocyte precursor cells but to date very little is known about myelin dynamics in vivo.
To improve the understanding of the process and realistically track the impact of intervention there is an essential
need for imaging techniques enabling to specifically quantify remyelination in vivo. Magnetic resonance imaging
(MRI) is the standard image biomarker for myelin but lacks of specificity. It is also influenced by water content,
oedema and inflammatory infiltration.
Recently studies have shown that [11C]PIB, a radiolabelled stilbene derivative for use with positron emission
tomography (PET), originally developed as biomarkers of amyloid plaques in Alzheimer’s disease, can be applied
to image myelin dynamics in MS patients. However, [11C]PIB has a short half-life and cannot be used clinically
as it requires an on-site cyclotron for production. Hence the main aim of this project is to repurpose commercially
available fluorinated stilbene and benzothiazole derivatives (Vyzamil – GE Healthcare; Neuraceq - Piramal;
AMYViD - Ely Lilli), currently used with PET to image amyloid deposits in dementia, as myelin imaging agents.
Furthermore, we wish to combine synergistically the specificity of these myelin markers with the high resolution
of MRI measures (magnetisation transfer imaging, diffusion-weighted imaging and T2-relaxometry) to obtain a
PET-MRI specific and sensitive in-vivo imaging assay.
Specifically this project aims to 1) Develop specific quantitative methodology to measure with Vyzamil,
Neuraceq and AMYViD myelin density in healthy volunteers and subjects with Multiple Sclerosis 2) to develop
a synergistic computational methodology to combine PET and MR myelin imaging modalities into a unique
multimodal assay. The work will be mainly computational and will exploit multiple datasets of PET and MRI
data for both healthy controls and patients with multiple sclerosis currently acquired at KCL and Imperial
College in on-going trials
Two representative publications from supervisors:
[1] Bodini B, Veronese M, Garcia-Lorenzo D, Battaglini M, Poirion E, Chardain, A, Freeman L, Louapre
C, Tchikviladze, Papeix C, Dolle F, Zalc B, Lubetzki c, Bottlaender M, Turkheimer F, Stankoff B. Dynamic
imaging of individual remyelination profiles in multiple sclerosis. Ann Neurol, 2016 Feb 18. doi:
10.1002/ana.24620
[2] Veronese M, Bodini B, Garcia-Lorenzo D, Battaglini M, Bongarzone S, Comtat C, Bottlaender M,
Stankoff B, Turkheimer F. Quantification of 11CPIB PET for myelin imaging in the human brain: a test-retest
reproducibility study in high resolution research tomograph. J Cereb Blood Flow Metab, 2015
Nov;35(11):1771-82.
16
12.4 Targeted radionuclide therapy: a new weapon in the war against microbial
multi-drug resistance
Co-Supervisor 1: Philip Blower
Research Division or CAG: ICAB
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/philip.blower.html
Co-Supervisor 2: Vincenzo Abbate
Research Division or CAG: IPS
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/vincenzo.abbate.html
Name of Collaborating Clinician: Dr. Nicholas M. Price FRCP PhD DTM&H
Research Division or CAG: Dept of Infectious Diseases, Guy's & St Thomas' NHS Foundation Trust
Email: [email protected]
Project description:
Bacterial multi-drug resistance is major threat to human health, making once-treatable diseases ever more
difficult to treat. This project will develop a new anti-microbial modality, borrowed from cancer treatment:
targeted radionuclide therapy or “molecular radiotherapy.” In this "Trojan Horse" approach, a radioisotope is
smuggled into bacterial cells exploiting their need for iron. Bacteria acquire their iron from the host by secreting
low molecular weight siderophores that scavenge ferric ions and shuttle them back inside the bacterium.
These siderophores also efficiently bind gallium, an element that has medically useful radionuclides for imaging
and molecular radiotherapy. 67Ga emits Auger electrons with a range commensurate with the size of bacterial
cells, and should therefore selectively kill the bacteria to which they are targeted. Thus, by administering 67Ga
as a siderophore complex, we envisage selectively killing bacteria while avoiding significant host toxicity. We
will synthesise siderophore analogues that bind to outer membrane receptors of both gram positive and gram
negative organisms, such as those in Figure 1. To prove the concept we will focus on infected vascular grafts and
stents, a significant clinical problem in cardiovascular surgery.
The project will suit a student with a first degree in biologically oriented chemistry. In year 1 or MRes rotation,
the candidate will assess the toxicity of 67Ga in bacteria, developing radiochemistry, radiobiology and
microbiology skills and knowledge of microbial multi-drug resistance. In year 2 the candidate will acquire
chemical synthesis and analytical skills by designing and preparing siderophore-analogues by a well-established
solid-phase route, and in years 3-4, test the efficacy of the new 67Ga complexes biologically and demonstrate
the concept.
Two representative publications from supervisors:
[1] Dual Selective Iron Chelating Probes with a Potential to Monitor Mitochondrial Labile Iron Pools
Abbate, V., Reelfs, O. S., Kong, X., Pourzand, C. & Hider, R. C. 2015 In : CHEMICAL
COMMUNICATIONS- ROYAL SOCIETY OF CHEMISTRY. 52, p. 784-787
[2] Ma MT, Cullinane C, Imberti C, Baguña-Torres J, Terry SYA, Roselt P, Hicks RJ, Blower PJ. New
tris(hydroxypyridinone) bifunctional chelators containing isothiocyanate groups provide a versatile platform for
rapid one-step labeling and PET imaging with 68Ga3+. Bioconjugate Chem 2016;27:309–318.
17
13.4 Improving stratification of valve stenosis through novel echocardiographic and
computational methods
Co-Supervisor 1: Dr. Pablo Lamata
Research Division/Department or CAG: Division of Imaging Sciences and Biomedical Engineering
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/pablo.lamata.html
Co-Supervisor 2: Dr. Robert Eckersley
Research Division/Department or CAG: Division of Imaging Sciences and Biomedical Engineering
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/robert.eckersley.html
Name of Collaborating Clinician: Prof. Mark Monaghan
Research Division/Department or CAG: Cardiovascular Clinical Academic Group
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/en/persons/mark-monaghan(2693c2a3-a6bb-4b9f-a460-
12d174c5b029).html
Project description:
Clinical problem: Valve stenosis is a cardiovascular condition where the valve does not open properly
Echocardiography has become the key tool for the diagnosis and evaluation of this condition, mainly thanks to
its non-invasiveness. The three main parameters extracted from this modality are the aortic jet velocity, the
transvalvular pressure drop (using the Bernoulli principle), and the valve area. Nevertheless, the assessment of
these variables is subject to limitations such as small imaging windows, shadowing or malalignments.
Hypothesis: Our recent research working with MRI has revealed a new factor that does improve the accuracy
of the widely adopted Bernoulli principle. The hypothesis is that echocardiographic data can provide the
necessary velocity information that will allow the translation of our findings, and thus improve the reliability and
accuracy of the pressure drop for the stratification of valve stenosis.
Objectives: the goal is to design a novel method to assess the severity of valve stenosis through the combination
of novel concepts in echocardiographic acquisition and computational fluid dynamics. Specifically, the student
will:
- Investigate the combination of continuous and colour Doppler sequences for the estimation of pressure
gradients through a novel computational formulation (year one).
- Investigate a complementary approach, using ultrafast planar wave imaging with contrast agents (year two).
- Design and validate the novel method, combining the strengths of the solutions explored (year three).
Background: the ideal candidate will have a BSc in Computer Science, Biomedical Engineering, Mathematics
or Physics.
Skills training: echocardiographic acquisition, reconstruction and analysis. Computational analysis skills in
order to assess pressure from echocardiographic data.
Two representative publications from supervisors:
[1] Non-invasive pressure difference estimation from PC-MRI using the work-energy equation. Med Image
Anal. 2015 26(1):159-172
[2] In vivo acoustic super-resolution and super-resolved velocity mapping using microbubbles. IEEE T Med
Imaging. 2015 34(2):433-440
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14.4 Cancer stem cell theranostics: Copper compounds for both diagnostic PET
imaging and chemotherapy
Co-Supervisor 1: Michelle Ma
Research Division or CAG: Division of Imaging Sciences (Faculty of Life Sciences and Medicine)
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/michelle.ma.html
Co-Supervisor 2: Kogularamanan Suntharalingam
Research Division or CAG: Department of Chemistry (Faculty of Natural and Mathematical Sciences)
Email: [email protected]
Website: http://www.kcl.ac.uk/nms/depts/chemistry/people/core/suntharalingamrama.aspx
Project description:
Cancer stem cells (CSCs) are a population of tumour cells linked to cancer relapse. CSCs self-renew, differentiate
and remain untouched by conventional therapies. Small molecules that target CSCs that can be combined with
conventional chemo-/radio-therapies have potential for more sustained responses in cancer patients. We have
shown that novel copper compounds bearing non-steroidal anti-inflammatory drugs can potently and selectivity
kill CSCs over bulk cancer cells. [1] They also demonstrate selectivity for hypoxic CSCs over normoxic cells.
Non-radioactive copper could be substituted for radioactive beta-emitting copper (Cu-64, Cu-62) in these
compounds. The avidity of the radioactive compounds for CSCs would remain the same, allowing for (i) whole-
body imaging of these compounds using Positron Emission Tomography (PET), and (ii) detailed studies on their
accumulation, retention and selectivity in different types of tissue (at the cellular, organ and whole-body level).
[2]
The student will prepare radioactive and nonradioactive copper compounds, enabling characterisation of their
biology in (i) CSC cultures, (ii) ex vivo models of hypoxia (collaboration with Dr Rick Southworth), and (iii)
mice bearing tumours with CSCs. This information will inform design of second-generation compounds. The
student will also probe the radioactive compounds’ potential to provide diagnostic CSC information at a whole-
body level using PET imaging. A diagnostic CSC PET radiopharmaceutical would have clinical impact,
particularly if coupled to a (nonradioactive) CSC chemotherapy.
This project is interdisciplinary, linking the Department of Chemistry with the Division of Imaging Sciences. It
involves chemical and radiochemical synthesis, biophysical analysis, molecular biology, and cellular and in vivo
imaging (PET). It will run in parallel to, and be financially co-supported by, a key component (PET metallomics)
of the proposed renewed Wellcome Medical Engineering Centre and a currently proposed Wellcome
Collaborative award on metallodrugs in cancer, as well as the current CRUK/EPSRC Cancer Imaging Centre
at King’s/UCL.
Two representative publications from supervisors:
[1] Boodram NJ, Mcgregor IJ, Bruno PM, Cressey PB, Hemann MT, Suntharalingam K, “Breast cancer
Stem cell potent copper(II)–non-steroidal anti-inflammatory drug complexes” Angewandte Chemie
International Edition, 2016, 55, 2845-2850.
[2] Ma MT, Cullinane C, Imberti C, Terry SYA, Roselt P, Hicks RJ, Blower PJ, “New
tris(hydroxypyridinone) bifunctional chelators containing isothiocyanate groups provide a versatile platform for
rapid one-step labeling and PET imaging with 68Ga3+”, Bioconjugate Chemistry, 2016, 27, 309-318.
19
15.4 Radiobiological assessment of radionuclide pairs used in theranostic (imaging
and therapy) approaches.
Co-Supervisor 1: Dr Samantha YA Terry
Research Division or CAG: Imaging Sciences and Biomedical Engineering
E-mail: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/samantha.terry.html
Co-Supervisor 2: Dr Lefteris Livieratos
Research Division or CAG: Department of Biomedical Engineering; Imaging and Biomedical Engineering CAG
and Department of Nuclear Medicine, Guy’s & St Thomas NHS FT
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/Lefteris.Livieratos.html
Project description:
Despite the use of radionuclides for imaging and therapy becoming more commonplace, their biological effects
are poorly understood. Little to no dosimetric or radiobiological considerations are taken into account when
radionuclides are administered and biological interpretation of dosimetry is still inaccurate. We do not know the
risks associated with multiple cycles of radionuclide imaging nor if radiopharmaceuticals are used to their
maximum therapeutic potential. Patients could potentially safely have more cycles of imaging and therapy than
currently supposed.
The aim is to determine the true safety of radionuclides for PET and SPECT imaging and when beta, alpha
particles and Auger electrons are most effective without harming healthy cells. Does cell localisation matter and
how for which radionuclides? Do neighbouring healthy cells act as if they too have been irradiated?
1. Expand and characterise a library of compounds with different cellular localisation properties using the
following combinations:
2. Study the biological effects
On and off target
Methods:
cell kill, miRNA and SNP signatures, DNA (a-b) and
chromosomal damage (c) and repair, reactive oxygen
and nitrogen species
In vitro (cells) and ex vivo (mice)
3. Dosimetry of above to determine absorbed doses
The combination of experimental radiobiology with localised dosimetry will aid the understanding of the
mechanisms involved in theranostics to inform the process of radiochemistry development (e.g. exclude non-
internalising agents labelled with Auger emitters below a certain energy threshold) and clinical translation (e.g.
redefine critical limits of organ absorbed dose for certain radiation emissions).
3. Dosimetry of above to determine absorbed doses
20
The combination of experimental radiobiology with localised dosimetry will aid the understanding of the
mechanisms involved in theranostics to inform the process of radiochemistry development (e.g. exclude non-
internalising agents labelled with Auger emitters below a certain energy threshold) and clinical translation (e.g.
redefine critical limits of organ absorbed dose for certain radiation emissions).
Two representative publications from supervisors:
[1] Relationship between chromatin structure and sensitivity to molecularly-targeted Auger electron
radiation therapy. Terry SYA and Vallis KA(2012) Int J Rad Onc Biol Phys 83:1298-305.
[2] Chuamsaamarkkee, K., Blower, P. J., & Livieratos, L. (2014). Dosimetric Evaluation based on
Preclinical Data of 188Re-Perrhenate versus 131I-Sodium Iodide for Improved Treatment of Benign Nodular
Thyroid Disease. Eur J Nuc Med Mol Imag 41, 280.
21
16.4 Nano-scale engineering of the stem cell niche to generate iPS-hepatocytes for
treatment of liver failure Co-Supervisor 1: Dr. Ciro Chiappini
Research Division or CAG: Department of Craniofacial Development and Stem Cell Biology
E-mail: [email protected]
Website: http://chiappiniliab.com
Co-Supervisor 2: Dr. Tamir Rashid
Research Division or CAG: Centre for Stem Cell Biology and Regenerative Medicine & Institute for Liver
Studies
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/tamir.rashid.html
Name of Collaborating Clinician (if not one of the two co-supervisors): Professor Reza Razavi
Research Division/Department or CAG: Imaging Sciences and Biomedical Engineering
Email: [email protected]
Website: https://kclpure.kcl.ac.uk/portal/reza.razavi.html
Project description:
Liver failure is a growing clinical burden claiming over 10,000 lives per year in the UK. Transplantation of
hepatocytes derived from iPSCs offers an appealing solution to this problem. To become clinically relevant,
maturation of progenitor cells currently generated is required. Since direct mechanical stimulation of the nucleus
can contribute to maturation by controlling gene expression we hypothesize this micro-environmental (niche)
cue is a critical missing factor in the process. This project will therefore combine direct stimulation of the nucleus
with organized 3-D culture to engineer a cell niche capable of maturing iPSCs into adult hepatocytes.
To achieve this, working as a valued member of our collaborative team, the student will develop a microfluidic
system to control confinement of the cell nucleus in three dimensions and assess the resulting epigenetic changes
at the chromatin, histone and DNA level. The epigenetic remodelling will be leveraged in combination with the
stimuli from the 3-D culture to direct maturation.
Techniques: Biomaterial design, microfluidics, 3-D culture, stem cell differentiation, advanced optical imaging,
cell/molecular biology, epigenetic & genetic analysis and rodent models of liver failure.
Rotation: Assess epigenetic remodelling induced by nuclear stimulation in existing microfluidic devices.
Year 1: Develop a novel microfluidic system for controlled and direct nuclear stimulation.
Year2: Induce controlled epigenetic remodelling through direct stimulation of the nucleus.
Year3: Develop a model of the hepatic niche combining direct nuclear stimulation with 3D culture & validate
the cell-niche product in pre-clinical rodent models of liver failure
Student Background:
The student will have a background in stem cell biology, molecular biology and microfluidic.
Two representative publications from supervisors:
[1] C. Chiappini, E. DeRosa, J.O. Martinez, X. Liu, J. Steele, M. Stevens, E. Tasciotti, Biodegradable
silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization, Nature
Materials 14, 532-539 (2015). http://bit.ly/1lABqFr
[2] Rashid & Yusa et al. Nature Targeted gene correction of α1-antitrypsin deficiency in induced
pluripotent stem cells, Nature 478, 391–394 (2011)
![Arbaeen'e Razavi [Urdu]](https://img.dokumen.tips/doc/110x75/577cdeb51a28ab9e78afa861/arbaeene-razavi-urdu.jpg)
